IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59155-w.html
   My bibliography  Save this article

Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes

Author

Listed:
  • Hongru Li

    (Nanjing Medical University)

  • Jingyi Zhao

    (Nanjing Medical University)

  • Jinglan Dai

    (Nanjing Medical University)

  • Dongfang You

    (Nanjing Medical University
    Nanjing Medical University)

  • Yang Zhao

    (Nanjing Medical University
    Key Laboratory of Biomedical Big Data of Nanjing Medical University)

  • David C. Christiani

    (Harvard University
    Harvard Medical School)

  • Feng Chen

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

  • Sipeng Shen

    (Nanjing Medical University
    Key Laboratory of Biomedical Big Data of Nanjing Medical University
    Nanjing Medical University)

Abstract

C-reactive protein (CRP) serves as a pivotal marker of systemic inflammation, yet its genetic architecture has predominantly been explored within European populations. Our multi-ancestry sequencing-based genome-wide association study (seqGWAS) meta-analysis encompasses 447,369 Europeans, 10,389 Africans, 9685 Asians, and 9200 Hispanics in the discovery set, and 23,521 Europeans, 7160 Africans, 771 Asians, and 5178 Hispanics in the replication set. We identify 113 independent association signals (Pdiscovery ≤ 5 × 10−9 and Preplication ≤ 0.05), including 21 loci that passed the conditional analysis, among which 3 are European-specific. Cross ancestry fine-mapping pinpoints 19 of 113 independent signals within the 95% credible set. Functional annotation reveals significant enrichment in blood tissue, H3K27me3 histone marks, and exonic regions. Leveraging the Polygenic Priority Score (PoPS) and gene-based analyses, we implicate 151 genes as potential regulators of CRP levels, 55 of which have not been previously reported. Among these, 17 genes and four proteins show causal evidence or strong colocalization with CRP-related pathologies.

Suggested Citation

  • Hongru Li & Jingyi Zhao & Jinglan Dai & Dongfang You & Yang Zhao & David C. Christiani & Feng Chen & Sipeng Shen, 2025. "Multi-ancestry sequencing-based genome-wide association study of C-reactive protein in 513,273 genomes," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59155-w
    DOI: 10.1038/s41467-025-59155-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59155-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-025-59155-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59155-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.